A key to understanding the function of any tissue is the biochemical characterization of the proteins that are specific to that tissue. Mammalian neural tissue is composed of two predominant cell types, neurons and glia, which are organized into a great variety of structures. Whether neural tissue is viewed as one or several tissues, its organization involves many cells that are believed generally to perform the same physiological actions but at different places and in response to different signals. Accordingly, one can expect to find a large number of neural tissue-specific proteins in both undifferentiated and differentiated neural tissue, including those involved in both specialized and general processes.
Exemplary of specifiable neural tissue-specific proteins are: neuropeptide precursors, enzymes responsible for neurotransmitter synthesis and/or processing, and proteins that participate in the release, degradation or reuptake of neurotransmitters, signal receptor systems and ion channels. Proteins included in the basic cellular structures encompass those peculiar to neurons (axons, dendrites and synapses) and those involved in establishing specific cell-cell interactions. Also, there will be proteins involved in mental processes such as memory which are not at all yet understood at the cellular, let alone molecular level. Clearly, nervous system tissue is a difficult tissue to study at the molecular level due to its great complexity.
Mature mammalian neurons are incapable of cell division and cannot, with the exception of olfactory neurons, be generated from stem cells in the adult nervous system. Thus, continuous dividing clonal cell lines with neuronal characteristics have proven to be very useful to neurobiologists studying almost every aspect of the nervous system. Such cell lines allow the generation of large numbers of homogeneous cells and the manipulation of these cells through gene transfer to yield novel derivatives expressing foreign gene products. These advantages have led to development and characterization of a variety of neuronal cell lines, some of which have been useful for cellular, biochemical, and molecular studies. The utility of these different cell lines and their ability to approximate aspects of the neuronal phenotype vary widely. Rapidly dividing neuronal cell lines usually do not possess the phenotypic properties of terminally differentiated non-dividing neurons, instead they often resemble in vivo neuroblasts or embryonic neurons. For example, many rapidly dividing cell lines elaborate immature neurites with an immature cytoskeleton. Naturally occurring neoplastic derivatives of many neuronal cell types of the central (CNS) and peripheral (PNS) nervous systems usually fall within this category (e.g., neuroblastomas, pheochromocytomas and medulloblastomas).
It is presumed that all of the proteins of the nervous system are synthesized by translation from specific messenger RNA (mRNA) molecules, and thus each neural tissue-specific protein must have a corresponding mRNA. Thus, one approach to the study of the nervous system is through the transcription pattern of mRNA molecules, or by asking the question of what messenger RNA species neural tissue produces relative to its complete genomic potential. Estimates for the complexity of mammalian neural tissue-specific mRNAs are very high; tens to hundreds of thousands of discrete mRNA molecules are implicated in nervous system function (Bantle et al., Cell, 8, 39-150, 1976, and Hastie et al., Cell 9, 761-774, 1976), consistent with the variety of neural tissue-specific proteins listed above.
It is an object of the invention to provide a unique protein marker of neural tissue, and a nucleic acid encoding the protein.
Yet another object of the invention is to provide a novel protein marker of certain neuronal tumor cell lines.
Yet another object of the invention is to provide a novel protein marker of both neuroblastoma and glioblastoma cells.
Yet another object of the invention is to provide a novel protein marker of cells of both the central and peripheral nervous system.
Yet another object of the invention is to provide antibodies specific for a novel protein marker present on neural tissue.
Another object of the invention is to provide probes for detection of a novel protein marker, or its corresponding mRNA, that is more abundant in normal neural tissue than in neoplastic tissue.